This invention relates to the treatment of tumors in animal hosts, such as human beings, and in particular provides a technique for destroying the tumor without injury to adjacent normal tissue. The tumors can be either benign or malignant and include carcinomas, sarcomas, cysts and avascular lesions.
It is an important object of this invention to provide an apparatus applicable to the treatment of tumors under a wide variety of conditions which can be utilized with a minimum, and preferably an absence, of surgery.
It has been noted that tumors can be affected by hyperthermia (Brit. of Cancer 25:771, 1971; Cancer Research 32:1916, 1972) and this observation was coupled with the notation that the tumors were heat sensitive. Experiments with external surface heating do not produce deep heating and in some cases, using hyperthermia, the whole animal was heated as much as the tumor. Others have felt that a slight raise in temperatures produced by metabolic changes in the cancer interfered with cell growth (Europ. J. Cancer 9:103, 1973). Still others have heated tumors for a few degrees by diathermy and observed that the effect on the tumor was inhibitory but not obstructive (Zeit. fur Naturforschung 8, 26:359, 1971). There is still disagreement in the role heat may play in the treatment of cancer (The Lancet, May 3, 1975; 1027).
Anatomical studies suggest that the blood flow through carcinomas and other neoplasms is sluggish (Acta Pathalogica Microbiologica Scand., 22:625, 1945; Advances in Biology of the Skin, 21:123, 1961). Furthermore, tumors possess an angiogenetic factor which initiates the formation of new blood vessels. These blood vessels, however, are capillaries which because of their small diameter offer great resistance to blood flow. The capillaries make connections with the normal capillaries on the periphery of the tumor and form tortuous haphazard pathways before emptying into some small vein at the periphery of the tumor. Frequently, there is marked venous obstruction within the tumor caused by compression of the peripheral veins due to enlargement of the tumor and sometimes due to ingrowth of tumor cells into the blood vessels obstructing them.
Anatomical studies also demonstrate the presence of arterio-venous fistulae at the periphery of tumors which can cause the tumors to appear vascular and angiographic because of the rapid appearance of contrast media, but which actually deprive the tumor of the blood supply. The arterio-venous fistulae at the periphery of the tumor tend to create a low resistance pathway at the surface of the tumor which lowers the arterial pressure and diverts blood from entering the tumor.
Although anatomical studies suggest that the tumor blood flow is diminished and slow, angiographic studies have functionally confirmed that blood flow through tumor is actually sluggish. Residual contrast medium remains in the tumor after it has been swept out of the adjacent normal tissue by normal blood flow. This remaining residual contrast medium has been called a "Tumor Stain". The tumors which have been studied radiographically have been brain tumors and kidney tumors.
This has been confirmed by the applicant by the indicator dilution technique measuring the actual flow of blood through normal tissue and through tumors. The indicator dilution technique is more reliable than the visual method as seen on angiography. Such studies were done in vivo using X-ray contrast medium dilution and in vivo on excised specimens. In the excised specimens blood flow was measured by indicator dilution technique using radioiodinated serum albumin. The albumin molecule was tagged with I.sub.131 and the isotope dilution was measured in the tumor and in normal tissue by a columnated scintillation counter. These studies indicated that the magnitude of flow through the adjacent normal tissue is such that the tumor tissue is differentially heated when the area of body containing the tumor is treated by diathermy.
It is known that tumors are usually destroyed by a quantum of heat which would be delivered by a temperature of 45.degree. C. over a period of three hours. Exposure at higher temperatures requires less time. At 50.degree. C., the time is reduced to a mere ten minutes. Such temperatures, of course, also destroy or severely damage normal tissue and the present invention utilizes Applicant's prior discovery that when a portion of the body is heated, for example, by applied radio frequency electromagnetic radiation, the tumor is heated differentially to a greater extent, such that the temperature of the normal tissue adjacent the tumor can be kept below 40.degree. C.
This effect is caused primarily by the normal blood flow in the adjacent normal, non-cancerous tissue, because the temperature at which tissue is heated is a function of the blood supply to the tissue. Although the blood itself is heated, it serves to carry heat away from the part being heated. Tissues which are poorly perfused with blood such as cancerous tissue become heated more rapidly and to a higher temperature than tissues which have a normal rate of blood flow. As pointed out above, cancerous and other malignant and benign growths develop outside a preformed blood distribution network and derive their blood supply from the periphery of the tumor where it meets the adjacent normal blood supply. As a consequence, the slow rate and volume of blood flow through the tumor provides a lessor cooling rate in &he tumor than the flow of blood through the normal tissues adjacent the tumor.
Such treatment of cancer has been fully disclosed in Applicant's U.S. Pat. No. Re. 32,066 dated Jan. 21, 1986 and the references cited therein.
The apparatus for heating tumors in the '066 patent employed an amplifier which amplified the output of a crystal oscillating at 13.56 or 27.12 megaHertz. Crystal oscillators are used to insure that the generated frequencies were within the band width allocated to medical use, otherwise it would be necessary to place the patient together with the R.F. generator into a Faraday cage to shield against leakage into the environment. However, studies on patients during R.F. treatment disclosed that the amount of R.F. in the immediate environment was usually greater than that permitted OSHA standards.
U.S. Pat. No. 4,285,346 describes an impedance matching unit which may be used between a radio frequency generator or source and a pair of electrodes placed adjacent a body. The patent also describes arrangements using a plurality of pairs of electrodes, pairs of which may be rendered separately inoperative by grounding of the transmission cable extending from the matching unit to a pair of electrodes.
U.S. Pat. No. 4,269,199 describes a method for inducing local hyperthermia in a tumor using an induction coil which is moved over a portion of the body containing the tumor such that the axis of the coil constantly transects different portions of the tumor.
Canadian Patent No. 1,177,895 describes dual and single coils which are excited in flux-aiding relationship over a small space in relation to the inside coil diameter. The inside diameter of the coils should be at least 1.5 times the diameter of the effective cell treatment zone and the coil spacing is substantially equal to the inside coil diameter which lends itself to testing on small animals and shallow seated cancer tumors.
U.S. Pat. No. 4,356,458 describes an apparatus for automatically adjusting the impedance of an electrical circuit connected to a radio frequency source so as to maintain the impedance of the circuit at a substantially constant value to permit the maximum transfer of energy to the load forming part of the circuit, and relates particularly to apparatus for use with the short wave diathermy apparatus described in the above-mentioned '346 patent.
U.S. Pat. No. 4,230,129 relates to apparatus for connecting radio frequency treatment equipment to the output of a body scanner or the like such that the exact position and configuration of the tumor can be plotted in terms of rectangular coordinates and the radio frequency equipment can then be directed or focused precisely on the tumor location in order to avoid excessive heating or thermal damage to the surrounding tissue. The applicator plates or discs are moved in an orbital manner such that the tumor always lies on the axis between the applicator plates and the radio frequency energy is concentrated therein. Because of the orbital movement of the applicators, the energy is not continuously being applied to a confined area, i.e., to immediately surrounding tissue but is rather applied over a comparatively large surface area so as not to affect the surrounding tissue adversely.